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Régulation du facteur de réplication de l'ADN MCM7 par poly-ubiquitinylation : rôles d'Int6 et BRCA1

Abstract : MCM7, one of the MCM DNA helicase subunits, is poly-ubiquitinated when it’s present on chromatin being replicated or repaired. During replication, MCM7 ubiquitination induces its degradation and departure from chromatin. The proto-oncoprotein Int6 interacts with ubiquitinated forms of MCM7 to protect them from degradation. Its absence induces MCM7 destabilisation and DNA damage. The Int6 capacity to regulate degradation of MCM7 and maybe of others factors, seems important for genomic stability. After an irradiation introducing DNA breaks, MCM7 is stabilized by ubiquitination, this process being stimulated by BRCA1, a tumor suppressor containing an ubiquitin ligase activity. This stabilization might participate to the MCM7 role in signalling DNA lesions. These results add MCM7 to the list of proteins of which ubiquitination regulates DNA metabolism to maintain genomic stability.
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https://tel.archives-ouvertes.fr/tel-00120941
Contributor : Samuel Buchsbaum <>
Submitted on : Tuesday, December 19, 2006 - 12:55:28 AM
Last modification on : Sunday, June 7, 2020 - 4:15:53 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 8:18:08 PM

Identifiers

  • HAL Id : tel-00120941, version 1
  • PRODINRA : 252092

Citation

Samuel Buchsbaum. Régulation du facteur de réplication de l'ADN MCM7 par poly-ubiquitinylation : rôles d'Int6 et BRCA1. Biochimie [q-bio.BM]. Ecole normale supérieure de lyon - ENS LYON, 2006. Français. ⟨tel-00120941⟩

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